1. Field of the Invention
The present invention relates generally to a method and formulation for measuring fat digestion and absorption and more specifically to a method and formulation for measuring fat digestion and absorption in individuals predisposed to inadequate fat digestion and absorption due to disease.
2. Background of the Invention
Certain diseases prevent persons from properly digesting and/or absorbing fat (triglycerides). For example, cystic fibrosis, the most common lethal genetic disorder of Caucasian populations, often results in a patient's inability to digest fat. This is due to the patient's pancreas being unable to supply the enzymes in sufficient amounts for hydrolysis. Another example is Celiac disease in which absorption of digested dietary fat is impaired due to reduced surface area of the small intestine.
Major advances in cystic fibrosis treatment have increased the life expectancy of patients with cystic fibrosis to more than 30 years. As no treatment is currently on the horizon to alleviate the pancreatic/gastrointestinal components of the disease, there is a growing population of cystic fibrosis patients who require life-long nutritional management. The diets of these patients generally are supplemented with pancreatic enzymes. To assure proper enzyme dosage, however, an accurate measurement of a patient's fat digestion and absorption is required.
A number of methods for determining the extent of fat digestion exist. For example, a direct and somewhat unpleasant method involves duodenal intubation and subsequent measurement of enzyme levels withdrawn from the intestine. The procedure is highly invasive, specialized, expensive and difficult to use in young children.
A myriad of indirect measurement procedures based on the appearance of a test substance in bodily fluids such as blood, urine, or breath are also available. These procedures have drawbacks, such as limitations related to the sampling compartment because of the underlying disease, and complications due to disease of related effects on other organ systems, such as the liver and the kidneys, which can lead to inaccurate results.
As an example of the limitations of current fat digestion and absorption measurement techniques, the problems inherent in the .sup.13 C-labeled fat breath test are highlighted below:
1.) Conversion rate of absorbed label to CO.sub.2 is influenced by the metabolic status of the individual. (e.g. liver function); PA1 2.) CO.sub.2 excretion is effected by lung function; PA1 3.) Variations in body fat content influence the rate of CO.sub.2 excretion; PA1 4.) Breath samples are not easily obtained from infants and young children; and PA1 5.) Long (6 to 12 hours) breath sampling times are required.
There are analogous limitations for tests which rely on the appearance of a test substance in blood or urine. Generally, appearance methods are unsuitable for quantitative measurements of gastrointestinal absorption of fat.
A widely used method for measuring fat absorption is the "72-hour stool fat test" (72-h SFT). This test requires that a patient consume 100 grams of fat daily for at least three days, during which the stools are collected for measurement of total fat content. The 72-h SFT is considered the "Gold Standard" for the purpose of determining a patient's ability to digest and/or absorb dietary fat.
However, there are many limitations to the 72-h SFT method. Overall, it is tedious and difficult to perform accurately. For example, a constant fat intake for at least three days is required. Also, quantitative collection of stools, (typically by the patient) is not assured. Only the most diligent adult patients supply accurate information regarding fat intake and accurate stool collection. Hospitalization and close monitoring is required for other adult patients, infants and children, which makes the procedure expensive. As a result, the 72 h SFT is most reliable to detect only significant steatorrhea (excessive fat in stool). Similarly, variability in the coefficient of fat absorption from test to test may be large.
A need exists in the art for an easy and economical method and formulation for directly measuring fat digestion and/or absorption under conditions of normal dietary intake. The method and formulation should depend neither on a patient's skill in collecting all stool for several days, nor in assuring constant fat intake for such a long period of time. The new method should be accurate, reliable, reproducible and noninvasive so as to facilitate easy monitoring and medical management of underlying disease. The results of the new method and formulation would be particularly useful in repetitive monitoring of changes in fat digestion as is recommended for patients with cystic fibrosis.